Colorectal CancerPhase 1NCT01420874
Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer)
A Phase 1 study testing FOLFOX6 and EGFRBi armed ATC Infusions in people with Colorectal Cancer and Cancer of Pancreas, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.
Trial summary
The purpose of this research study is for the participant to give their own T cells (a type of blood cell in the body that can fight infections and possibly cancer) to them after they have been removed, grown in a lab, and then coated with an experimental drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm
- What is being tested?
- FOLFOX6 and EGFRBi armed ATC Infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Aug 2011to 19 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological or cytological proof of colorectal or pancreatic adenocarcinoma
- Must have metastatic colorectal cancer or pancreatic cancer with stable disease after first line chemotherapy or patients with colorectal or pancreatic cancer who have progressed with standard chemotherapy options*
- Standard chemotherapy for metastatic colorectal cancer include 5-FU/capecitabine with either oxaliplatin or irinotecan based regimen with or without bevacizumab or cetuximab.
- Standard chemotherapy for metastatic pancreatic cancer include gemzar based regimen or FOLFIRINOX (5-FU, oxaliplatin, and irinotecan)
- Prior cetuximab, panitumumab, or other monoclonal antibody therapy allowed if given 28 days prior to the 1st infusion of armed T cells
- Absolute Neutrophil Count (ANC) ≥ 1,000/mm3
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- Lymphocyte count ≥ 400/mm3
- Platelet Count ≥ 50,000/mm3
- Hemoglobin ≥ 8 g/dL
- Serum Creatinine < 2.0 mg/dl, Creatinine Clearance ≥50 ml/mm (can be calculated)
- Total Bilirubin ≤ 2 mg/dl (biliary stent is allowed)
- SGPT and SGOT < 5.0 times normal
- LVEF ≥ 45% at rest (MUGA or Echo)
- Pulse Oximetry of >88%
- Age ≥ 18 years at the time of consent
- Written informed consent and HIPAA authorization for release of personal health information
- Females of childbearing potential, and males, must be willing to use an effective method of contraception
- Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy
- KPS ≥ 70% or SWOG Performance Status 0 or 1
Who cannot join
- Any chemotherapy related toxicities from prior treatment.(> grade I per CTCAE v4.0
- Known hypersensitivity to cetuximab or other EGFR antibody
- Treatment with any investigational agent within 14 days prior to being registered for protocol therapy Protocol version: 07/13/2011 8
- Symptomatic brain metastasis
- Chronic treatment with systemic steroids or another immuno-suppressive agent
- Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
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- Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- HIV infection
- Positive HbsAg
- Positive Hepatitis C
- Active bleeding or a pathological condition that is associated with a high risk of bleeding
- Uncontrolled systemic disease like active infections
- Nonmalignant medical illnesses that are uncontrolled or a controlled illness that may be jeopardized by the treatment with protocol therapy
- Females must not be breastfeeding
- Patient may be excluded if, in the opinion of the PI and investigator team, the patient is not capable of being compliant
- Minor changes from these guidelines will be allowed at the discretion of the attending team under special circumstances. The reasons for exceptions will be documented.
Trial locations and contacts
1 site in 1 country.
United States1 site
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48601
About this study
Official title: Treatment of Advanced Colorectal or Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Armed Activated T-Cells (Phase Ib)
The purpose of this research study is for the participant to give their own T cells (a type of blood cell in the body that can fight infections and possibly cancer) to them after they have been removed, grown in a lab, and then coated with an experimental drug.
This study will determine the highest dose of EGFR2Bi coated T cells that can be given without causing severe side effects. Initially a group of 3 participants will receive the same dose of study drug. If no serious side effects occur, the next group of participants will receive a slightly higher dose of study agent. The following groups of participants will receive higher doses of the study drug until a dose is reached where there are unacceptable side effects and maximum tolerated dose is found, or the planned highest dose level is reached with no side effects.
Read the detailed description
The purpose of this study is to determine in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi armed activated T cells (aATC), after chemotherapy, for patients with advanced colorectal and pancreatic cancer
- Conditions
- Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma
- Being tested
- FOLFOX6, EGFRBi armed ATC Infusions
- Medical subject headings
- Colorectal Neoplasms, Pancreatic Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOX6Drug
Also called leucovorin (FOLinic acid), Fluorouracil, OXaliplatin
IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line) for continuous infusion of 5-FU. Adv. colorectal and pancreatic pts. w/no other standard chemo available, \& in pts who cannot receive FOLFOX chemo, immunotherapy may be given w/o antecedent chemo.
EGFRBi armed ATC InfusionsBiological
Armed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subsequent doses will be administered once weekly, for 3 weeks, then 12 weeks post aATC#1. Dose escalation level(per infusion): Level 0-5 billion; Level 1-10 billion; Level 2-20 billion; Level 3-40 billion
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX6 & EGFRBi armed ATC Infusions | Experimental | FOLFOX6: IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line) for continuous infusion of 5-FU. Adv. colorectal and pancreatic pts. w/no other standard chemo available, \& in pts who cannot receive FOLFOX chemo, immunotherapy may be given w/o antecedent chemo.
EGFRBi armed ATC Infusions: Armed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subsequent doses will be administered once weekly, for 3 weeks, then 12 weeks post aATC#1. Dose escalation level(per infusion): Level 0-5 billion; Level 1-10 billion; Level 2-20 billion; Level 3-40 billion Receives: Drug: FOLFOX6; Biological: EGFRBi armed ATC Infusions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determining in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi aATC, and a booster infusion after 3 months, for patients with advanced colorectal or pancreatic cancer.
Participants will be assessed for changes in lab values (CBC, Sodium, potassium, calcium, magnesium, chloride, bicarbonate, glucose,BUN, creatinine, total Protein, albumin, total bilirubin, ALP, AST,ALT, CEA or CA 19-9.
Measured: 4 wks after chemo, prior to ATC infusion #2; 1 wk later prior to ATC infusion #3; Wks 2, 4 & 9 post ATC infusion #3; Wk 8 post ATC #4 (booster)
Secondary outcomes (3)
Determining whether IMT enhances anti-tumor immunity;Cytokine resp., phenotypic markers, anti-tumor cytotoxicity, in vivo and in vitro specific anti-tumor antibody prod. & molecular signaling markers of T-cell activation assessed before chemo & after IMT
Immune studies: Serum cytokine responses will be quantified focus on the levels of those factors known to be important regulators of T cell responses. Phenotype analysis will measure the percent of T, B, NKT and NK cells in peripheral blood mononuclear cell (PBMC) and tumor-infiltrating lymphocyte (TIL) samples. T cell proportions would be further analyzed by subset (CD4, CD8, CD25+). Cytotoxicity is measured in percentage in PBMC.
Measured: 3 weeks after chemo prior to ATC infusion #1; At wks 4(ATC #2) & 5 (ATC #3) post chemo; wks 2 , 4 & 9 post ATC #3 infusion; Day of ATC #4 (booster infusion), then wks 2, 4 & 8; & mon 6 and 1yr post ATC #4 (booster infusion)
Determining the tumor response rate
CT or PET Scan
Measured: Approximately every 8 weeks to until 1 year
Overall Survival
CT or PET Scan
Measured: Approximately every 8 weeks to until 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2011 (estimated)
- Study start17 Aug 2011
- Primary completion19 Oct 2020
- Study completion19 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anthony F. Shields, MD PhD, Barbara Ann Karmanos Cancer Institute
- Investigators
- Anthony Shields, M.D. PhD, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01420874
- Sponsor's protocol ID
- 2011-025
- Status last verified
- May 2023
- First submitted
- 17 Aug 2011
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lum LG, Thakur A, Choi M, Deol A, Kondadasula V, Schalk D, Fields K, Dufrense M, Philip P, Dyson G, Aon HD, Shields AF. Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. Oncoimmunology. 2020 Jun 10;9(1):1773201. doi: 10.1080/2162402X.2020.1773201.
PubMed 32939319
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Advanced Colorectal or Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Armed Activated T-Cells (Phase Ib)
- ClinicalTrials.gov ID
- NCT01420874
- Acronym / sponsor ID
- 2011-025
- Conditions
- Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Study start
- 17 Aug 2011 (actual)
- Primary completion
- 19 Oct 2020 (actual)
- Study completion
- 19 Oct 2020 (actual)
- First posted
- 22 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is for the participant to give their own T cells (a type of blood cell in the body that can fight infections and possibly cancer) to them after they have been removed, grown in a lab, and then coated with an experimental drug.
This study will determine the highest dose of EGFR2Bi coated T cells that can be given without causing severe side effects. Initially a group of 3 participants will receive the same dose of study drug. If no serious side effects occur, the next group of participants will receive a slightly higher dose of study agent. The following groups of participants will receive higher doses of the study drug until a dose is reached where there are unacceptable side effects and maximum tolerated dose is found, or the planned highest dose level is reached with no side effects.
Detailed description
The purpose of this study is to determine in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi armed activated T cells (aATC), after chemotherapy, for patients with advanced colorectal and pancreatic cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFOX6 & EGFRBi armed ATC Infusions | Experimental | Drug: FOLFOX6, Biological: EGFRBi armed ATC InfusionsFOLFOX6: IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line) for continuous infusion of 5-FU. Adv. colorectal and pancreatic pts. w/no other standard chemo available, \& in pts who cannot receive FOLFOX chemo, immunotherapy may be given w/o antecedent chemo. EGFRBi armed ATC Infusions: Armed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subsequent doses will be administered once weekly, for 3 weeks, then 12 weeks post aATC#1. Dose escalation level(per infusion): Level 0-5 billion; Level 1-10 billion; Level 2-20 billion; Level 3-40 billion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histological or cytological proof of colorectal or pancreatic adenocarcinoma
- Must have metastatic colorectal cancer or pancreatic cancer with stable disease after first line chemotherapy or patients with colorectal or pancreatic cancer who have progressed with standard chemotherapy options*
- Standard chemotherapy for metastatic colorectal cancer include 5-FU/capecitabine with either oxaliplatin or irinotecan based regimen with or without bevacizumab or cetuximab.
- Standard chemotherapy for metastatic pancreatic cancer include gemzar based regimen or FOLFIRINOX (5-FU, oxaliplatin, and irinotecan)
- Prior cetuximab, panitumumab, or other monoclonal antibody therapy allowed if given 28 days prior to the 1st infusion of armed T cells
Key exclusion criteria (16 listed)
- Any chemotherapy related toxicities from prior treatment.(> grade I per CTCAE v4.0
- Known hypersensitivity to cetuximab or other EGFR antibody
- Treatment with any investigational agent within 14 days prior to being registered for protocol therapy Protocol version: 07/13/2011 8
- Symptomatic brain metastasis
- Chronic treatment with systemic steroids or another immuno-suppressive agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FOLFOX6Also: leucovorin (FOLinic acid), Fluorouracil, OXaliplatinIV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line) for continuous infusion of 5-FU. Adv. colorectal and pancreatic pts. w/no other standard chemo available, \& in pts who cannot receive FOLFOX chemo, immunotherapy may be given w/o antecedent chemo. | Drug | FOLFOX6 & EGFRBi armed ATC Infusions |
| EGFRBi armed ATC InfusionsArmed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subsequent doses will be administered once weekly, for 3 weeks, then 12 weeks post aATC#1. Dose escalation level(per infusion): Level 0-5 billion; Level 1-10 billion; Level 2-20 billion; Level 3-40 billion | Biological | FOLFOX6 & EGFRBi armed ATC Infusions |
Primary outcome
Determining in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi aATC, and a booster infusion after 3 months, for patients with advanced colorectal or pancreatic cancer.
Time frame: 4 wks after chemo, prior to ATC infusion #2; 1 wk later prior to ATC infusion #3; Wks 2, 4 & 9 post ATC infusion #3; Wk 8 post ATC #4 (booster)
Participants will be assessed for changes in lab values (CBC, Sodium, potassium, calcium, magnesium, chloride, bicarbonate, glucose,BUN, creatinine, total Protein, albumin, total bilirubin, ALP, AST,ALT, CEA or CA 19-9.
3 secondary outcomes
Determining whether IMT enhances anti-tumor immunity;Cytokine resp., phenotypic markers, anti-tumor cytotoxicity, in vivo and in vitro specific anti-tumor antibody prod. & molecular signaling markers of T-cell activation assessed before chemo & after IMT
Time frame: 3 weeks after chemo prior to ATC infusion #1; At wks 4(ATC #2) & 5 (ATC #3) post chemo; wks 2 , 4 & 9 post ATC #3 infusion; Day of ATC #4 (booster infusion), then wks 2, 4 & 8; & mon 6 and 1yr post ATC #4 (booster infusion)
Determining the tumor response rate
Time frame: Approximately every 8 weeks to until 1 year
Overall Survival
Time frame: Approximately every 8 weeks to until 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Derived from this study: PubMed 32939319Lum LG, Thakur A, Choi M, Deol A, Kondadasula V, Schalk D, Fields K, Dufrense M, Philip P, Dyson G, Aon HD, Shields AF. Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. Oncoimmunology. 2020 Jun 10;9(1):1773201. doi: 10.1080/2162402X.2020.1773201.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Shields, M.D. PhD principal investigator
Barbara Ann Karmanos Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FOLFOX6 and EGFRBi armed ATC Infusions in people with Colorectal Cancer and Cancer of Pancreas, run by Barbara Ann Karmanos Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determining in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi aATC, and a booster infusion after 3 months, for patients with advanced colorectal or pancreatic cancer. (time frame: 4 wks after chemo, prior to ATC infusion #2; 1 wk later prior to ATC infusion #3; Wks 2, 4 & 9 post ATC infusion #3; Wk 8 post ATC #4 (booster)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01420874, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.